2-Trifluoroacetylthiophene oxadiazoles as potent and selective class II human histone deacetylase inhibitors.
Trifluoroacetylthiophene carboxamides have recently been reported to be class II HDAC inhibitors, with moderate selectivity. Exploration of replacements for the carboxamide with bioisosteric pentatomic heteroaromatic like 1,3,4-oxadiazoles, 1,2,4-oxadiazoles and 1,3-thiazoles, led to the discovery that 2-trifluoroacetylthiophene 1,3,4-oxadiazole derivatives are very potent low nanomolar HDAC4 inhibitors, highly selective over class I HDACs (HDAC 1 and 3), and moderately stable in HCT116 cell culture.
Muraglia
Ester
E
IRBM-Merck Research Laboratories Rome, Via Pontina km 30,600-Pomezia, 00040 Rome, Italy. ester_muraglia@merck.com
Altamura
Sergio
S
Branca
Danila
D
Cecchetti
Ottavia
O
Ferrigno
Federica
F
Orsale
Maria Vittoria
MV
Palumbi
Maria Cecilia
MC
Rowley
Michael
M
Scarpelli
Rita
R
Steinkühler
Christian
C
Jones
Philip
P
D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D045325:HCT116 Cells; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000145:classification; D006801:Humans; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D056572:Histone Deacetylase Inhibitors; D010069:Oxadiazoles; D013876:Thiophenes; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases